The Navajo Nation was heavily mined for uranium from the 1940s through the 1980s, resulting in the premature death of hundreds of Dine miners from occupational lung cancers and non-malignant respiratory diseases. Community members, health-care providers, and tribal leaders worry that broader public health impacts have resulted from environmental exposures to >1,000 abandoned mining and milling sites. Yet, no epidemiological evaluation of community health and exposures has occurred in mining-impacted communities. That uranium and other trace metals are strong nephrotoxicants has focused community concerns on the possible relationship between environmental agents and the high prevalence of chronic renal insufficiency in the Eastern Navajo Agency. In addition to anthropogenic exposures from mining, milling, and living near mine and mill sites, most community members haul drinking water from unregulated sources and can be exposed to uranium through ingestion. Whether these exposures combine with other risk factors such as diabetes to increase the prevalence of chronic kidney disease (CKD) in the population remains unknown. The proposed Navajo Uranium Assessment and Kidney Health Project (NUAKHP) was developed at the request of, and in collaboration with, the leading community-based health advisory body - the Eastern Navajo Health Board (ENHB) - and is the result of several years of planning and training of tribal members. The first aim of this five-year study to is reduce uranium exposures due to drinking water from unregulated water sources by assessing water quality and usage in 100 water sources in 20 Navajo communities in northwestern New Mexico, and working with the communities and the tribal utility authority to develop acceptable, safe alternatives. The second aim will calculate relative risks for CKD in the local population from ingestion of uranium and other kidney toxicants from unregulated water sources in combination with other environmental uranium exposures, occupational histories, and socio-economic, cultural, and health risk factors. Community-level surveys and medical records reviews will be used to assess human use of unregulated water sources and behavioral, socioeconomic and cultural factors contributing to this usage in 1,000 participants. In a subset of 450, kidney health will be assessed through standard clinical blood screening methods and analyses of urinary biomarkers for early detection of kidney impairment. A subset of participants will be followed at two years to develop pilot data on biomarkers and disease progression in relation to exposure. These studies will strengthen research capacity within the Navajo Nation, reduce uranium exposure, and inform development of a local kidney health surveillance system. This work will also establish norms for kidney disease biomarkers in the Navajo population, and for the first time assess contribution of kidney toxicants to progression of kidney disease in an at-risk population